Patients with end stage renal disease undergo frequent hemodialysis to remove toxins from the blood and maintain appropriate homeostasis. In dialysis, blood is withdrawn from a vascular access, purified, and returned to a vein or a synthetic graft. The two most common forms designed to enable long-term vascular access in chronic hemodialysis patients are the native arteriovenous (AV) fistula and an AV shunt.
In the AV fistula method, openings are created in an artery and vein, usually in the arm above or below the elbow. The borders of the openings are attached to form an anastomosis at which the vein is joined to the artery and provide a common passageway, conventionally referred to as a fistula, through which blood flows directly from the artery to the vein. The arterial blood pressure, being higher than the venous pressure, together with the supra-physiological flow rates, eventually enlarges the vein and a “mature” and a functioning vascular access is created 2-4 months post procedure. The mature vascular access enables sufficient blood flow rate, effective dialysis procedure and the accommodation of a cannula or large needles.
Hemodialysis vascular access dysfunction is a contributing factor to morbidity in hemodialysis patients. According to Roy-Chaudhury et al., “Vascular access in hemodialysis: issues, management, and emerging concepts” (in Cardiology Clinics 23, 2005: 249-223) there are several causes of failures of vascular access procedures. Roy-Chaudhury et al. identifies two main causes of such failure in AV fistulae as maturation failure and early venous stenosis, both are caused by development of neointimal hyperplasia which includes thickening of the tunica media and the tunica intima (a smooth muscle wall and endothelial layer in the vessel) due to inward proliferation of cells.
Maturation failure and early venous stenosis may be caused by the development of a juxta-anastomotic stenosis due to the neointimal hyperplasia in propinquity to the artery-vein anastomosis. According to Roy-Chaudhury et al., an initiating event in the pathogenesis of venous stenosis in AV dialysis is hemodynamic stress, especially in regions of low shear stress and turbulence in the vicinity of the fistula. Another initiating event is the high wall tension to which the vein graft is exposed. Under normal physiological conditions, the pressure in the venous circulation is 3-5 mmHg. After fistula creation, the mean pressure in the vein is 100 mmHg. Unlike arteries, veins have relatively thin wall with thin muscularis layer. As a compensation reaction, while trying to adapt to the “new” physiological conditions and high pressures, the vein wall thickens in an attempt to reduce the sudden high wall tension. The pathological process of wall thickening is considered the seed of intimal hyperplasia and vein stenosis.